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Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory T-cell Lymphoma or Hodgkin Lymphoma

NCT03302728

Description:

This study is investigating the combination of Brentuximab vedotin and lenalidomide in the treatment of relapsed/refractory peripheral T cell lymphoma or cutaneous T cell lymphoma or Hodgkin lymphoma. It is hypothesised that lenalidomide may augment the actions of Brentuximab vedotin in these patient groups. The primary objective of the study is to determine the maximum tolerated dose of the combination treatment, which can be used in subsequent studies. The study will also investigate disease response and survival. Participants will receive Brentuximab vedotin (once every 21 days i.e. 1 cycle) and lenalidomide (daily from day 1 -14 of each cycle) for a maximum of 48 weeks and will be followed for a subsequent 6 months after the end of treatment.

Related Conditions:
  • Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory T-cell Lymphoma or Hodgkin Lymphoma
  • Official Title: A Phase 1b Study of Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-cell Lymphoma, CD30-positive Peripheral T-cell Lymphoma, or CD30-positive Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 17/34
  • NCT ID: NCT03302728

Conditions

  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Lenalidomide 15mgRevlimidLenalidomide & brentuximab vedotin
Brentuximab Vedotin 1.8 mg/KgAdcetrisLenalidomide & brentuximab vedotin

Purpose

This study is investigating the combination of Brentuximab vedotin and lenalidomide in the treatment of relapsed/refractory peripheral T cell lymphoma or cutaneous T cell lymphoma or Hodgkin lymphoma. It is hypothesised that lenalidomide may augment the actions of Brentuximab vedotin in these patient groups. The primary objective of the study is to determine the maximum tolerated dose of the combination treatment, which can be used in subsequent studies. The study will also investigate disease response and survival. Participants will receive Brentuximab vedotin (once every 21 days i.e. 1 cycle) and lenalidomide (daily from day 1 -14 of each cycle) for a maximum of 48 weeks and will be followed for a subsequent 6 months after the end of treatment.

Trial Arms

NameTypeDescriptionInterventions
Lenalidomide & brentuximab vedotinExperimentalBrentuximab vedotin 1.8mg/Kg Lenalidomide 15 mg
  • Lenalidomide 15mg
  • Brentuximab Vedotin 1.8 mg/Kg

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients of 18 years or older.

          2. Patient must have a diagnosis of a CD30+ Hodgkin Lymphoma or CD30+ peripheral T-cell
             lymphoma. Patients with either Hodgkin lymphoma or T-cell lymphoma must have
             expression of CD30 in ≥10% of lymphoma cells. Patients with CTCL will be considered
             for inclusion even if CD30 immunohistochemical staining with BerH2 antibody is low or
             negligible (<10%).

               1. Peripheral T-cell lymphoma: patients must be considered relapsed or refractory
                  after at least one prior chemotherapeutic regimen or be considered by the
                  investigator to be not suitable for chemotherapy

               2. Cutaneous T-cell lymphoma: patients must be relapsed or refractory to one prior
                  systemic therapy or be considered by the investigator to be not suitable for
                  chemotherapy

               3. Patients with Hodgkin lymphoma and one of the following:

             i. Relapsed or refractory after at least 2 prior chemotherapy-containing regimens
             ii.Considered unsuitable for chemotherapy

          3. Voluntary written informed consent must be given before performance of any study-
             related procedure.

          4. Female patient is either post-menopausal for at least 1 year before the screening
             visit or surgically sterile or if of childbearing potential, agree to practice 2
             effective methods of contraception, at the same time, from the time of signing the
             informed consent through 6 months after the last dose of study drug, or agrees to
             completely abstain from heterosexual intercourse.

          5. Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to
             practice effective barrier contraception during the entire study period and through 6
             months after the last dose of study drug, or agrees to completely abstain from
             heterosexual intercourse.

          6. Performance status of ECOG ≤2.

          7. Clinical laboratory values as specified below. Blood tests must be within 10 days of
             patient registration:

               -  Absolute neutrophil count >1.5 x109/L, or >1.0 x109/L in the setting of known
                  marrow involvement by tumour.

               -  Platelet count ≥75x109/L.

               -  Total bilirubin must be < 1.5 x the upper limit of the normal (ULN) unless the
                  elevation is known to be due to Gilbert syndrome.

               -  ALT or AST must be < 2.5 x the upper limit of the normal range. AST or ALT may be
                  elevated up to 5 times the ULN if their elevation can be reasonably ascribed to
                  the presence of haematologic/solid tumor in liver.

               -  Serum creatinine must be < 150 µmol/L and/or creatinine clearance or calculated
                  creatinine clearance > 40 mL/minute.

               -  Haemoglobin must be ≥ 80g/L.

          8. Patients must have fully recovered from the acute toxic effects of all prior
             chemotherapy, immunotherapy, or radiotherapy (except alopecia) prior to registration.

        Exclusion Criteria:

          1. Female patients who are both lactating and breast-feeding or have a positive serum
             pregnancy test during the screening period or a positive pregnancy test on planned
             cycle 1, day 1 prior to first dose of study drug.

          2. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to the protocol.

          3. Symptomatic neurologic disease compromising normal activities of daily living or
             requiring medication/s, including signs or symptoms of Progressive Multifocal
             Leucoencephalopathy (PML).

          4. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2 at
             registration.

          5. Known history of any of the following cardiovascular conditions

               1. New York Heart Association (NYHA) Class III or IV heart failure (see Appendix
                  18.1).

               2. Evidence of current uncontrolled cardiovascular conditions, including cardiac
                  arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic
                  evidence of acute ischemia or active conduction system abnormalities.

               3. A left-ventricular ejection fraction <50%

          6. Any active systemic viral, bacterial, or fungal infection requiring systemic
             intravenous antibiotics or systemic antifungal therapies within 2 weeks prior to
             registration.

          7. Patients that have not completed any prior treatment chemotherapy and/or other
             investigational agents within at least 5 half-lives of last dose of that prior
             treatment.

          8. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient
             contained in the drug formulation of brentuximab vedotin or lenalidomide.

          9. Known human immunodeficiency virus (HIV) positive.

         10. Known hepatitis B surface antigen (HBsAg)-positive, or known or suspected active
             hepatitis C infection. Patients who are Hepatitis B core antibody positive with no
             evidence of active disease, i.e.

             HBsAg negative/ negative hepatitis B viral load, will still be considered eligible for
             inclusion, but must receive viral suppressive therapy for the duration of the trial.

         11. Active systemic malignancy likely to require treatment within the next two years, or
             previous diagnosis of another malignancy with residual disease. Patients with
             non-melanoma skin cancer or carcinoma- in-situ of any type are not excluded if they
             have undergone complete resection.

         12. Previous exposure to brentuximab vedotin.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of the combination of lenalidomide and brentuximab vedotin
Time Frame:70 weeks
Safety Issue:
Description:Maximum tolerated dose, dose-limiting toxicities of the combination therapy, and recommended phase 2 dose, in patients with relapsed/refractory cutaneous T-cell lymphoma, CD30-positive Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma. The MTD is defined as the highest dose level at which the incidence of DLT was less than 33%.

Secondary Outcome Measures

Measure:Safety profile of the combination of lenalidomide and brentuximab vedotin
Time Frame:70 weeks
Safety Issue:
Description:Toxicities measured using CTCAE V4.03.
Measure:Treatment intensity.
Time Frame:48 weeks
Safety Issue:
Description:Treatment intensity defined as the actual total dose received divided by the actual treatment period.
Measure:Objective response rate
Time Frame:70 weeks
Safety Issue:
Description:Objective response, defined as achieving either complete response (CR) or partial response (PR) at some stage from time of commencement of treatment until conclusion of period of follow-up (maximum 16 cycles of treatment followed by 6 months of follow-up), or until time of documented progressive disease (defined as clinical and/or radiologic progression).
Measure:Cytostatic response.
Time Frame:70 weeks
Safety Issue:
Description:Cytostatic response, defined as achieving complete response (CR), partial response (PR) or stable disease (SD) lasting >6 months from time of commencement of treatment until progressive disease (PD).
Measure:Event free survival.
Time Frame:70 weeks
Safety Issue:
Description:Event free survival (EFS), defined as the time from commencement of treatment to date of early discontinuation of treatment due to toxicity, date of documented disease progression at any site, or date of death from any cause, whichever occurs first.
Measure:Overall survival
Time Frame:70 weeks
Safety Issue:
Description:Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Peter MacCallum Cancer Centre, Australia

Trial Keywords

  • CD 30 positive, relapsed, refractory

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